RESUMO
OBJECTIVES: This study aimed to determine the role of T1 mapping in identifying cardiac allograft rejection. BACKGROUND: Endomyocardial biopsy (EMBx), the current gold standard to diagnose cardiac allograft rejection, is associated with potentially serious complications. Cardiac magnetic resonance (CMR)-based T1 mapping detects interstitial edema and fibrosis, which are important markers of acute and chronic rejection. Therefore, T1 mapping can potentially diagnose cardiac allograft rejection noninvasively. METHODS: Patients underwent CMR within 24 h of EMBx. T1 maps were acquired at 1.5-T. EMBx-determined rejection was graded according to International Society of Heart and Lung Transplant (ISHLT) criteria. RESULTS: Of 112 biopsies with simultaneous CMR, 60 were classified as group 0 (ISHLT grade 0), 35 as group 1 (ISHLT grade 1R), and 17 as group 2 (2R, 3R, clinically diagnosed rejection, antibody-mediated rejection). Native T1 values in patients with grade 0 biopsies and left ventricular ejection fraction >60% (983 ± 42 ms; 95% confidence interval: 972 to 994 ms) were comparable to values in nontransplant healthy control subjects (974 ± 45 ms; 95% confidence interval: 962 to 987 ms). T1 values were significantly higher in group 2 (1,066 ± 78 ms) versus group 0 (984 ± 42 ms; p = 0.0001) and versus group 1 (1,001 ± 54 ms; p = 0.001). After excluding patients with an estimated glomerular filtration rate <50 ml/min/m2, there was a moderate correlation of log-transformed native T1 with high-sensitivity troponin T (r = 0.54, p < 0.0001) and pro-B-type natriuretic peptide (r = 0.67, p < 0.0001). Using a T1 cutoff value of 1,029 ms, the sensitivity, specificity, and negative predictive value were 93%, 79%, and 99%, respectively. CONCLUSIONS: Myocardial tissue characterization with T1 mapping displays excellent negative predictive capacity for the noninvasive detection of cardiac allograft rejection and holds promise to reduce substantially the EMBx requirement in cardiac transplant rejection surveillance.
Assuntos
Edema Cardíaco/diagnóstico por imagem , Rejeição de Enxerto/diagnóstico por imagem , Transplante de Coração/efeitos adversos , Imagem Cinética por Ressonância Magnética , Adulto , Aloenxertos , Biópsia , Estudos de Casos e Controles , Estudos Transversais , Edema Cardíaco/imunologia , Edema Cardíaco/patologia , Edema Cardíaco/fisiopatologia , Feminino , Fibrose , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/imunologia , Miocárdio/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Adulto JovemRESUMO
BACKGROUND: Immune activation in patients with chronic heart failure may be secondary to endotoxin (lipopolysaccharide) action. We investigated the hypothesis that altered gut permeability with bacterial translocation and endotoxaemia would be increased in patients with oedema secondary to congestive heart failure. METHODS: We compared 20 patients who had chronic heart failure with recent-onset peripheral oedema (mean age 64 years [SD 10], New York Heart Association [NYHA] class 3.3 [0.7]), 20 stable non-oedematous patients with chronic heart failure (mean age 63 years [19], NYHA class 2.6 [0.7]), and 14 healthy volunteers (mean age 55 years [16]). Biochemical markers of endotoxaemia, inflammation, and immune activation were measured. Ten patients were studied within 1 week of complete resolution of oedema. Five patients survived longer than 6 months and were restudied again after remaining free of oedema for more than 3 months. FINDINGS: Mean endotoxin concentrations were higher in oedematous patients with chronic heart failure than in stable patients with chronic heart failure (0.74 [SD 0.45] vs 0.37 EU/mL [0.23], p=0.0009) and controls (0.46 EU/mL [0.21], p=0.02). Oedematous patients had the highest concentrations of several cytokines. After short-term diuretic treatment, endotoxin concentrations decreased from 0.84 EU/mL [0.49] to 0.45 EU/mL [0.21], p<0.05) but cytokines remained raised. After freedom of oedema for more than 3 months after oedema resolved, endotoxin concentrations remained unchanged from the previous visit (0.49 EU/mL [0.06], p=0.45). INTERPRETATION: Raised concentrations of endotoxin and cytokines are found in patients with chronic heart failure during acute oedematous exacerbation. Intensified diuretic treatment can normalise endotoxin concentrations. Our preliminary findings suggest that endotoxin may trigger immune activation in patients with chronic heart failure during oedematous episodes.